High-voltage catheters for sub-microsecond pulsing

ABSTRACT

Described herein are flexible catheters adapted to be inserted into a body to deliver high-voltage, fast (e.g., microsecond, sub-microsecond, nanosecond, picosecond, etc.) electrical energy to target tissue. Also disclosed herein systems including these catheters and method of using them to treat tissue.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to U.S. Provisional PatentApplication No. 62/806,750, filed on Feb. 15, 2019, titled “HIGH-VOLTAGECATHETERS FOR SUB-MICROSECOND PULSING,” and herein incorporated byreference in its entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference in their entirety to the sameextent as if each individual publication or patent application wasspecifically and individually indicated to be incorporated by reference.

FIELD

Described herein are apparatuses (e.g., devices, systems, etc.) andmethods that may be used to perform medical operations to treatpatients. Specifically, the apparatuses described herein can includeminimally invasive devices, such as catheters, endoscopes, laparoscopes,etc. that may apply high-voltage, short electrical pulses to treatpatients.

BACKGROUND

Short, high-field strength electric pulses have been described forelectroperturbation of biological cells. For example, electric pulsesmay be used in treatment of human cells and tissue including tumorcells, such as basal cell carcinoma, squamous cell carcinoma, andmelanoma. The voltage induced across a cell membrane may depend on thepulse length and pulse amplitude. Pulses longer than about 1 microsecondmay charge the outer cell membrane and lead to opening of pores.Permanent openings may result in instant or near instant cell death.Pulses shorter than about 1 microsecond may affect the cell interiorwithout adversely or permanently affecting the outer cell membrane andresult in a delayed cell death with intact cell membranes. Such shorterpulses with a field strength varying in the range of 10 kV/cm to 100kV/cm may trigger apoptosis (i.e. programmed cell death) in some or allof the cells exposed to the described field strength and pulse duration.These higher electric field strengths and shorter electric pulses may beuseful in manipulating intracellular structures, such as nuclei andmitochondria. For example, sub-microsecond (e.g., nanosecond) highvoltage pulse generators have been proposed for biological and medicalapplications.

Because of the very high therapeutic voltages, as well as the very fastpulse times, applicators for delivery of such nanopulse energy devicesmust be configured so as to avoid damaging tissues or otherwise harmingthe patient. The risks of delivering high-voltage energy, such risksincluding electrical shock, arcing, burns, internal-organ damage, andcardiac arrhythmias, are even more acute when the high-voltage device isintended to be inserted into the body.

Thus, it would be beneficial to provide devices, such as catheters,endoscopes, laparoscopes, etc. that may apply high-voltage, short (alsoreferred to as “fast”) electrical pulses to treat patients whileaddressing the above-mentioned risks.

SUMMARY OF THE DISCLOSURE

Described herein are apparatuses (including systems and devices, such ascatheters, endoscopes, laparoscopes, etc.) and methods for the treatmentof a patient that may use them to more effectively apply therapeuticenergy, including but not limited to short, high field strength electricpulses, while avoiding the risk of arcing or otherwise harming thetissue. These applicators may be particularly well suited, for example,for treatments of various disorders and diseases, such as, but notlimited to cancer (and other types of abnormal tissue growth), and thelike. These applications may be also particularly well suited for usewith various fully and partially automated systems, such as roboticsystems.

In particular, the apparatuses described herein may be configured assingle-use catheters that can be used with a variety of differentre-usable generator systems, as will be described in greater detailherein.

Furthermore, the apparatuses described herein may be integrated intosystems that are configured to be mounted onto or coupled to a roboticarm of a robotic system, such as robotic medical treatment system orrobotic surgical system. While for convenience of description thepresent disclosure may refer to the robotic surgical system, however, itshould be understood that such robotic surgical system is intended tocover any robotic medical treatment system (including for cosmeticapplications) and may include robotic systems having guidance. In somevariations instruments can be guided and controlled by the roboticsurgical system during a surgical procedure. For example, the devicesdescribed herein may be used through one or more operating channels of arobotic system. Examples of robotic systems that may be modified for useas described herein (and/or may be used with or may include any of thesefeatures) are described in U.S. patent application Ser. No. 15/920,389“TREATMENT INSTRUMENT AND HIGH-VOLTAGE CONNECTORS FOR ROBOTIC SURGICALSYSTEM,” filed on Mar. 13, 2018, which is hereby incorporated byreference in its entirety for all purposes.

According to one aspect, apparatuses described herein comprise cathetersand scopes (e.g., endoscopes, laparoscopes, etc.) that may include a tiphaving a plurality of electrodes that may be retractable and/or mayinclude a retractable/removable insulating region that may protect andinsulate one or more treatment electrodes (e.g., plate electrodes,needle electrodes, etc.) through which high-voltage rapidly pulsedenergy may be delivered into the tissue. These apparatuses may beconfigured safely and reliably to deliver microsecond or sub-microsecond(e.g., nanosecond, picosecond, etc.) pulses, and may include an electricfield with a sub-microsecond pulse width of between 0.1 nanoseconds (ns)and 1000 nanoseconds, or shorter, such as 1 picosecond, which may bereferred to as sub-microsecond pulsed electric field. This pulsed energymay have high peak voltages, such as 1 kilovolts per centimeter (kV/cm),2-3 kV/cm, 5 kV/cm, 10 kV/cm, 20 kV/cm, 50 kV/cm, to 500 kV/cm.Treatment of biological cells may use a multitude of periodic pulses ata frequency ranging from 0.1 per second (Hz) to 10,000 Hz, and maytrigger apoptosis, for example, in the diseased tissue or abnormalgrowth, such as cancerous, precancerous or benign tumors. Selectivetreatment of such tumors with high-voltage, sub-microsecond pulsedenergy can induce apoptosis within the tumor cells without substantiallyaffecting normal cells in the surrounding tissue due to its non-thermalnature. A subject may be a patient (human or non-human, includinganimals). A user may operate the apparatuses described herein on asubject. The user may be a physician (doctor, surgeon, etc.), medicaltechnician, nurse, or care provider.

Thus, the application of high-voltage, fast (e.g., microsecond,nanosecond, picosecond, etc.) electrical pulses may include applying atrain of sub-microsecond electrical pulses having a pulse width, forexample, of between 0.1 nanoseconds (ns) and 1000 nanoseconds. Applyinghigh-voltage, fast electrical pulses may include applying a train ofsub-microsecond electrical pulses having peak voltages of between, forexample, 1 kilovolts per centimeter (kV/cm) and 100 kV/cm. Applyinghigh-voltage, fast electrical pulses may include applying a train ofsub-microsecond electrical pulses at a frequency, for example, ofbetween 0.1 per second (Hz) to 10,000 Hz.

For example, described herein are apparatuses for treating tissue. Forexample, these apparatuses may include: an elongate body comprising: afirst conductive layer formed from a first plurality of braided or wovenfilaments extending down at least a portion of the length of theelongate body; a second conductive layer formed from a second pluralityof braided or woven filaments extending concentric to the firstconductive layer; wherein the first and second conductive layers areenclosed by a flexible electrically insulating material; a firstelectrode at a distal end region of the catheter in electricalcommunication with the first conductive layer; a second electrode at thedistal end region of the catheter in electrical communication with thesecond conductive layer; and a high-voltage connector adapted to couplethe first and second conductive layers to a pulse generator.

Any of these apparatuses may include one or more lumens. For example theapparatuses described herein may include a guidewire lumen that isconcentrically surrounded by the first and second conductive layers. Theguidewire lumen may be configured to fit any standard guidewire (orguide catheter). The guidewire lumen may include a lubricious coating orcover (e.g., Teflon). This lumen may also or alternatively be configuredas a working channel for passing one or more additional instruments. Thesame or other (e.g., additional) lumen may be used for any otherpurpose, including visualization (e.g., deploying a fiber optic, camera,etc.), delivery and/or removal of material (drug, conductive gel,saline, conducive fluid, etc.), vacuum, etc. For example, in somevariations a lumen extending the length of the apparatus may deliverconductive fluid and/or gel to the region at or around the electrodes.In some variations the outlet for the lumen may be positioned at or nearthe electrodes; for example the outlet(s) of the one or more lumenconfigured to carry conductive fluid may be positioned adjacent to(around, beside, and/or between) the one more electrodes on theapparatus.

These apparatuses may be configured as catheters. Some embodiments ofthe present disclosure provide an advantageous and unique combination ofa concentric configuration, a plurality of layers and an ability towithstand high voltages, which provides flexibility desired for thecatheters while accommodating size limitations or geometric constrains,improving safety and minimizing noise.

The first and second electrodes may be separated by 0.5 mm or more(e.g., 0.8 or more, 1 mm or more, 2.0 mm or more 3.0 mm or more 3.2 mmor more 3.5 or more, 4 mm or more, 4.5 mm or more, 5 mm or more, 6 mm ormore, etc.).

In general, the first and second conductive layers are configured toconduct high-voltage, fast pulses of electrical energy. The first andsecond conductive layers may also be configured to modify the mechanicalproperties of the catheter. For example, the first conductive layer maycomprise a first braid pattern of conductive filaments that varies alonga distal to proximal length of the catheter so that the catheter is moreflexible at the distal end. For example, the braided pattern may have adifferent braid angle along the length of the catheter. In somevariations the braid angle may increase along the proximal-to-distallength; in some variations the braid angle may decrease along theproximal-to-distal length. The braid angle may vary constantly or by onemore steps. In some variations, the second conductive layer comprises asecond braid pattern of conductive filaments that also varies along thedistal to proximal length of the catheter. In some variations thepattern of filaments in the first conductive layer is different than thepattern of filaments in the second conductive layer. For example, thepattern of braided or woven filaments in the first conductive layer maybe a mirror image of the pattern of braided or woven filaments in thesecond conductive layer.

Any of the apparatuses described herein may include a bias (e.g., on anouter surface of the distal end region of the apparatus) that isconfigured to drive the distal end region of the catheter against avessel wall when deployed in a vessel. Any appropriate bias may be used(e.g., spring, such as a leaf spring, coil spring, etc., an inflatableballoon, a shape-memory alloy, etc.).

The flexible insulating material may have a dielectric strengthsufficient to withstand 1 or 2 kV or more, 3 kV or more, 5 kV or more(e.g., 7 kV or more, 8 kV or more, 9 kV or more, 10 kV or more, 12 kV ormore, 15 kV or more, etc.). More than one flexible insulating material(e.g., having different dielectric strengths) may be used; including asuse in different regions, such as around the first and second (or more)conductive layers. For example, the first and second conductive regionsmay be surrounded by a high dielectric strength material than otherportions of the catheter.

Any of these apparatuses (e.g., catheters) may include one or moresteering tendons (or wires) within a lumen of the elongate body. Thetendons may be fixed at one end region (e.g., to the distal end regionof the guidewire) and otherwise free to move within a lumen in the bodyof the apparatus.

The apparatuses described herein may include any appropriatelyconfigured electrodes, including one or more of: needle electrodes,plate electrodes, ring electrodes, surface electrodes, knife electrodes,etc. The electrodes may be static (e.g., present on the surface orconfigured to extend from the surface) and/or they may be dynamic (e.g.,configured to extend from the body of the device and/or retract into thedevice). For example, the first and second electrodes comprise needleelectrodes. The electrodes may be positioned on a distal end face of theapparatus (e.g., catheter) and/or they may be positioned on a lateralside of the elongate body.

In some variations a system for treating tissue may include: a cathetercomprising: an elongate body having a first conductive layer formed froma first plurality of filaments extending down at least a portion of thelength of the elongate body, a second conductive layer formed from asecond plurality of filaments extending concentric to the firstconductive layer, wherein the first and second conductive layers areenclosed by a flexible insulating material having a dielectric strengthsufficient to withstand 1 kV or more, for example, 5 kV or more; a firstelectrode at a distal end region of the catheter in electricalcommunication with the first conductive layer; a second electrode at thedistal end region of the catheter in electrical communication with thesecond conductive layer; and a high-voltage connector adapted to couplethe first and second conductive layers to a pulse generator configuredto generate a plurality of electrical pulses having amplitude of atleast 0.1 kV and a duration of less than 1000 nanoseconds.

Any of the apparatuses or systems may include a pulse generator. Forexample, also described herein are systems for treating tissue, thesystem comprising: a catheter comprising: an elongate body having afirst conductive layer formed from a first plurality of filamentsextending down the length of the elongate body, a second conductivelayer formed from a second plurality of filaments extending concentricto the first conductive layer, wherein the first and second conductivelayers are enclosed by a flexible insulating material having adielectric strength sufficient to withstand 1 kV or more; a firstelectrode at a distal end region of the catheter in electricalcommunication with the first conductive layer; a second electrode at thedistal end region of the catheter in electrical communication with thesecond conductive layer; a pulse generator configured to generate aplurality of electrical pulses having amplitude of at least 0.1 kV and aduration of less than 1000 nanoseconds; and a high-voltage connectorconfigured to connect to the pulse generator through a port, thehigh-voltage connector adapted to couple the first and second conductivelayers to the pulse generator. Examples of pulse generators that may bemodified or use as described herein are shown, for example in U.S.patent application Ser. No. 15/269,273 “HIGH VOLTAGE CONNECTORS ANDELECTRODES FOR PULSE GENERATORS,” filed on Sep. 19, 2016, which ishereby incorporated by reference in its entirety for all purposes.

Also described herein are methods of using any of the apparatuses (e.g.,catheters), for example, to treat tissue. Generally these catheters maybe configured to treat tissue within a body by delivering, through thecatheter, one or a train of high-voltage, fast (e.g., sub-millisecond,nanosecond, picosecond) pulses. For example, the catheters and systemsof the present disclosure may be used in various cardiac applications,esophageal applications, methods of treatment of the lung tissue, orbronchial passages. Also, the methods of the present disclosure includethe methods of therapeutic treatment, including cosmetic treatments. Ingeneral, a cosmetic treatment may include treatment of skin or othertissue within a body. Cosmetic treatments may be applied to change orenhance a user's appearance. Although many of the examples describedherein are specific to methods of treatment (including cosmetic methods)the methods described herein may be used for non-treatment purposes,including testing of the catheter, experimental purposes (e.g.,inserting the catheter into a model of a body), etc.

For example, described herein are methods of treating tissue, the methodcomprising: inserting a distal end of a catheter into a body, whereinthe catheter comprises at least two electrodes at a distal end region;applying a plurality of electrical pulses having an amplitude of greaterthan 0.1 kV and a duration of less than 1000 nanoseconds to a proximalend of the catheter through a first plurality of filaments extending atleast partially down the length of the catheter and through a secondplurality of filaments extending at least partially down the length ofthe catheter; and delivering the applied plurality of electrical pulsesto the body from a first electrode of the at least two electrodes inelectrical communication with the first plurality of filaments and asecond electrode of the at least two electrodes in electricalcommunication with the second plurality of filaments, wherein the firstand the second plurality of filaments is configured and insulated towithstand 1 kV or more. The second plurality of filaments may extendconcentrically over the first plurality of filaments. In someembodiments, the first and the second plurality of filaments may beconfigured and insulated to withstand 2 kV or more, 3 kV or more, 5 kVor more, or 9 kV or more.

Also described herein are methods of delivering pulsed power to any ofthe apparatuses described herein, including in particular to a catheter.For example, a method may include: connecting a high-voltage connectorto a first conductive layer and a second conductive layer of a catheter,the first conductive layer formed from a first plurality of filamentsextending down at least a portion of a length of an elongate body of thecatheter, the second conductive layer formed from a second plurality offilaments extending concentric to the first conductive layer; andapplying a plurality of electrical pulses having an amplitude of 1 kV ormore from the high-voltage connector through the first plurality offilaments and through the second plurality of filaments, wherein thefirst and second conductive layers are insulated by a flexibleinsulating material having a dielectric strength sufficient to withstand1kV or more. In some embodiments the electrical pulses may have anamplitude of between 1 kV and 15 kV, or between 1 kV and 9 kV, orbetween 3 kV and 5 kV, or any sub-range within the above ranges.

Any of these methods may also include connecting the catheter to a pulsegenerator using a high-voltage connector. The high voltage connector mayinclude a lip, rim, skirt, ridge, etc. and/or a standoff region. In somevariations the high-voltage connector may include one or more interlocksconfigured to prevent energy from being applied through the connectoruntil sealing contact is ensured (e.g., by applying a low-power signalthrough and determining the stability of the connection, e.g., viaimpedance or other electrical property.

Inserting may comprise inserting the catheter over a guide wire using aguide wire lumen passing concentrically through the first and secondplurality of filaments, for example, braided or woven filaments. Theguidewire may be used to guide (position) the catheter, for example, toa location within a body.

Any of these methods may also include driving the distal end of thecatheter against the tissue so that the first and second electrodescontact the tissue. For example, driving may include inflating aninflatable balloon on a side of the distal end of the catheter.

As described above, at least one or both of the first and secondplurality of filaments may comprise braided or woven filaments. Thearrangement of the first and second plurality of filaments may beconfigured to reduce loop currents (electrical field leakage).

The methods described herein may include checking impedance between afirst electrode (e.g., at a distal end region of the catheter) inelectrical communication with the first conductive layer and a secondelectrode (e.g., at the distal end region of the catheter) in electricalcommunication with the second conductive layer. The impedance may bechecked or monitored either prior to and/or while applying the pluralityof electrical pulses. The impedance may be used to control operation ofthe apparatus and in particular the impedance may be used to turn onand/or off the application of electrical energy to the apparatus. Forexample, any of these methods may include periodically or continuouslychecking impedance between the first and second electrodes during theapplication of the plurality of electrical pulses and stopping orsuspending the application, for example, if the impedance falls below animpedance threshold or, alternatively, exceeds an impedance threshold,or suspending application of electrical pulses until the impedanceexceeds an impedance threshold.

The apparatuses and methods described herein are generally configuredfor bipolar operation, e.g., wherein the apparatus includes two or more(e.g., groups) of electrodes between which the electrical energy isapplied to generate a therapeutic electric field, as described herein.However, in some variations the apparatuses and devices described hereinmay be configured to be operated as monopolar devices in which a singleelectrode (or group of electrodes) is used to apply energy from thedevice, and the electrical return is a remote one or more electrodes,including a second apparatus, an external electrode, such as anelectrical patch or pad. In some variations the apparatuses descriedherein may be configured to apply electrical energy between a firstelectrode or group of electrodes on an apparatus (e.g., catheterapparatus as described herein) and a remote electrode or group ofelectrodes. Any of the apparatuses described herein may be operated as amonopolar apparatus even where multiple electrodes are included, forexample, by operating multiple electrodes as a group (e.g., electricallyconnecting their outputs).

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the present disclosure are set forth withparticularity in the claims that follow. A better understanding of thefeatures and advantages of the present disclosure will be obtained byreference to the following detailed description that sets forthillustrative embodiments, in which the principles of the disclosure areutilized, and the accompanying drawings of which:

FIG. 1 schematically illustrates one example of a system, including acatheter, for delivery of high-voltage, fast pulsed electrical energy.

FIG. 2 illustrates an example of a pulse profile for voltage and currentthat may be applied by the apparatuses described herein.

FIGS. 3A and 3B schematically illustrate examples of electrodes arrangedto deliver high-voltage (e.g., 15 kV), fast (e.g., sub-millisecond)pulses of electrical energy into a tissue from the distal end of acatheter.

FIG. 3C illustrates one example of voltage versus time chart for asystem delivering fast electrical energy (e.g., high voltage,sub-microsecond pulsing).

FIG. 4 is an example of a cross-section of a catheter configured fordelivering high voltage, fast pulses of electrical energy.

FIG. 5 is an example of a cross-section of a catheter configured fordelivering high voltage, fast pulses of electrical energy.

FIG. 6 is an example of a cross-section of a catheter configured fordelivering high voltage, fast pulses of electrical energy.

FIG. 7A and 7B schematically show cross-sections of examples ofcatheters with outer insulating jackets.

FIGS. 8A-8D show examples of catheters (shown in cross-section)including one (FIGS. 8A and 8C) or more (FIG. 8B and 8D) steeringtendons or pull wires.

FIGS. 9A and 9B show another example of a high-voltage catheter inlongitudinal section (FIG. 9A) and in cross-section (FIG. 9B) includinga pair of steering tendons on opposite sides of the catheter.

FIG. 9C shows the catheter of FIGS. 9A and 9B being steered.

FIG. 10A shows an example of a cross-section of the distal end of acatheter configured for the delivery of high-voltage, fast pulsedelectrical energy including an inflatable tip biasing element.

FIG. 10B shows the catheter of FIG. 10A with the inflatable tip-biasingelement un-inflated. FIG. 10C shows the catheter of FIG. 10A with theinflatable tip-basing element inflated.

FIG. 11 is an example of a catheter configured for the delivery ofhigh-voltage, fast pulses for use in an atrial ablation.

FIGS. 12A-12C are examples of a distal tip region, including electrodesof a catheter configured for the delivery of high-voltage, fast pulses.

FIG. 13 shows yet another example of a catheter instrument which may beused to deliver high-voltage, fast pulses of electrical energy.

FIG. 14A and FIG. 14B show examples of high-voltage connectorsconfigured to be mated with a housing of a pulse generator (shown as acutaway portion), before mating (FIG. 14A) and after mating (FIG. 14B).

FIG. 15A shows a cross-sectional view of an example of a high-voltageconnector and a portion of a housing of a pulse generator (shown as acutaway portion).

FIG. 15B shows a cross-section of a high-voltage connector and a housingcutaway portion with the connector engaged.

FIG. 15C shows an enlarged higher-detailed view of the engagement of ahigh-voltage connector.

FIG. 15D shows a cross-section of a high-voltage connector and a housingcutaway portion with the connector engaged, and with a minimum clearancedistance shown.

FIG. 16 is an illustration of a high-voltage connector configured to bemated with a pulse generator housing (shows as a partial cutawayportion).

FIG. 17A shows a cross-section of a high-voltage connector and a portionof a housing (shown as a partial cutaway).

FIG. 17B is an illustration of a cross-sectional view of a high-voltageconnector and a cutaway view of a portion of a pulse generator housing.

FIG. 18 illustrates an example of a high-voltage connector that may beused to couple a catheter to a pulse generator configured for thedelivery of high voltage, fast pulses as described herein.

DETAILED DESCRIPTION

Described herein are flexible catheters adapted to be inserted into abody to deliver high-voltage, fast (e.g., microsecond, nanosecond,picosecond, etc.) electrical energy to target tissue. Apparatuses andsystems described herein are especially useful in high-voltagesub-microsecond pulsing applications. Therefore, for convenience ofdescription, these catheters will be described herein, by example, inreference to high-voltage, sub-microsecond catheters.

FIG. 1 illustrates one example of a system 100 for deliveringhigh-voltage, fast pulses of electrical energy that includes a catheter102 and a pulse generator 107, footswitch 103, and user interface 104.Footswitch 103 is connected to housing 105 (which may enclose theelectronic components) through connector 106. The catheter 102 mayinclude the electrodes and is connected to housing 105 and theelectronic components therein through a high voltage connector 112. Thehigh-voltage system 100 may also include a handle 110 and storage drawer108. The system 100 may also include a holder (e.g., holster, carrier,etc.—not shown) which may be configured to hold the catheter 102.

A human operator may input a number of pulses, amplitude, pulseduration, and frequency information, for example, into a numeric keypador a touch screen of interface 104. In some embodiments, the pulse widthcan be varied. A microcontroller may send signals to pulse controlelements within system 100. In some embodiments, fiber optic cablesallow control signaling while also electrically isolating the contentsof the metal cabinet with generation system 100, e.g., the high voltagecircuit, from the outside. In order to further isolate the system,system 100 may be battery powered instead of from a wall outlet.

FIG. 2 illustrates an example of a pulse profile for both voltage andcurrent for a high-voltage, fast (e.g., sub-microsecond) pulsing. FIG. 2illustrates examples of output from the system 100 with voltage shown inthe top portion of the figure and the current shown on the bottomportion of the figure, showing a first and second pulses. The firstpulse has an amplitude of about 15 kV, a current of about 50 A, and aduration of about 15 ns. The second pulse has an amplitude of about 15kV, a current of about 50 A, and a duration of about 30 ns. Thus, insome examples, 15 kV may be applied to electrodes connected to thesystem having 4 mm between the plates so that the target tissueexperiences 37.5 kV/cm (e.g., 15 kV/0.4 cm), and current between 12 and50 A. Given a voltage, current depends heavily on the electrode type andtissue resistance.

While FIG. 2 illustrates one specific example, other pulse profiles mayalso be generated. For example, in some embodiments, rise and/or falltimes for pulses may be less than 20 ns, about 20 ns, about 25 ns, about30 ns, about 40 ns, about 50 ns, about 60 ns, about 75 ns, or greaterthan 75 ns. In some embodiments, the pulse voltage may be less than 5kV, about 5 kV, about 10 kV, about 15 kV, about 20 kV, about 25 kV,about 30 kV, or greater than 30 kV. In some embodiments, the current maybe less than 10 A, about 10 A, about 25 A, about 40 A, about 50 A, about60 A, about 75 A, about 100 A, about 125 A, about 150 A, about 175 A,about 200 A, or more than 200 A. In some embodiments, the pulse durationmay be less than 10 ns, about 10 ns, about 15 ns, about 20 ns, about 25ns, about 30 ns, about 40 ns, about 50 ns, about 60 ns, about 75 ns,about 100 ns, about 125 ns, about 150 ns, about 175 ns, about 200 ns,about 300 ns, about 400 ns, about 500 ns, about 750 ns, about 1 μs,about 2 μs, about 3 μs, about 4 μs, about 5 μs, or greater than 5 vs. Inaddition, in some embodiments the pulses may alternate from a positiveamplitude to a negative amplitude in a biphasic manner, for example, thefirst pulse could be +1 kV followed by second pulse at −1 kV, or a firstpulse at +3 kV followed by a second pulse at −2 kV.

FIGS. 3A and 3B schematically illustrate examples of electrodes shown atthe distal end of a catheter 301 (shown as perpendicularly extending orextendable needle or knife electrodes that may penetrated into thetissue. In FIG. 3A, the exemplary electrode extends 2 mm from thecatheter into the tissue and form a row that is 5 mm long. More than onerow of electrodes (arranged, e.g., in the long axis of the catheterand/or at an angle, including 90 degrees to the long axis) may beincluded. For example, multiple (e.g., two, three, etc.) rows ofelectrodes, e.g., 0.5 mm long electrodes, 1 mm long electrodes, 1.5 mmlong electrodes, 2 mm long electrodes, etc. may be provided. Further,the space between electrodes may be shorter or longer than 1 mm (e.g.,0.5 mm, 1 mm, 1.5 mm or longer, 2 mm or longer, 2.5 mm or longer, 3 mmor longer, 3.5 mm or longer, 4 mm or longer, 4.5 mm or longer, 5 mm orlonger, etc.). For example, FIG. 3B shows an example of a catheter 301having a pair of extending/extendable electrodes 305 that are separatedby 5 mm or more. In some variations the electrodes may be separated byan insulting barrier (border, ring, etc.) between, around and/oradjacent to the electrodes.

In some variations the apparatus may be configured for monopolaroperation and may include just a single electrode (not shown) or mayelectrically couple multiple electrodes. For example, in FIG. 3A, theprotruding electrodes 305 may act as a single pole (e.g., singleelectrode). Thus, any of these apparatuses may be used with a remoteelectrode (a return or electrical ground electrode, not shown). Forexample, in some variations the remote electrode (electrical return) maybe a grounding pad on which a subject (e.g., patient) may lie. Thegrounding pad (or external ground) may be a conductive mesh. In general,a grounding pad may be of any appropriate material(s). Alternatively, insome variations the remote electrical return may be applied to an outersurface of the body or within the body in another location or region.Thus, any of the apparatuses and systems described herein, including thesub-microsecond pulsed, high voltage apparatuses, may be monopolar, ormay be applied between separate devices. Thus, although relatively highfields may be generated between the source electrode, e.g., on anapparatus as described herein, and a return electrode, such as a groundpad, surface (e.g., skin) electrode and/or second device (e.g., adifferent catheter device).

When the device is operated in a monopolar configuration the resultingfield may be directed or steered by positioning the return electrode sothat target tissue region is between the electrode on the apparatus andthe ground electrode. In some cases the target tissue region may beadjacent to the electrode on the apparatus. For example, in somevariations the methods and apparatuses described herein may be used totreat a cardiac tissue, such as an epicardial, endocardial, and/orpericardial tissue. In one monopolar embodiment, the apparatus, such asa catheter apparatus with a first electrode, may be positioned withinthe heart (e.g., at or near the target region of the heart) and thereturn electrode may be a ground pad, for example, a pad that thesubject is lying on. In another monopolar embodiment the apparatus withthe first electrode (or a group of electrodes) may be positioned withinthe heart and the return electrode may be positioned on the subject'sskin, e.g., above the heart, below the heart, or other remote location,in order to direct the field between the electrodes on the catheter andthe return electrode, through the target tissue.

Any of the apparatuses described herein may also be used forcatheter-to-catheter treatments, in which the first catheter includingone or more (grouped) electrodes, as described herein, and a second(return) catheter including one or more (grouped) electrodes may bepositioned on an opposite side of the target region of the tissue. Forexample, a cardiac treatment may include positioning a first catheterapparatus as described herein in a first chamber of the heart and asecond catheter apparatus as described herein in a second chamber of theheart, and applying energy to generate a therapeutic field between thetwo, e.g., passing through the target tissue (e.g., a septal wall).

FIG. 3C shows another example of a pulse train that may be delivered bya system (e.g., high-voltage, fast pulsing electrical generator andcatheter for delivery thereof). In particular, FIG. 3C shows an exampleof a voltage vs. time graph for sub-microsecond pulsing using a 15 kVpeak for pulses 321 of 300 ns. The pulses may be repeated at a desiredrepetition rate 325, such as, e.g., between 0.1 Hz and 25 kHz or more.Thus, the apparatuses, including systems, described herein may include apulse generator such as the one shown schematically in FIG. 1,configured to emit pulses in the sub-microsecond range, similar to theoutput parameters described above.

In general, these apparatuses may include a high-voltage connector forsafely connecting the catheter device to a high-voltage power source.Examples of high-voltage connectors are provided below and described indetail in reference to FIGS. 14-19 below. As described above, thesecatheters are configured to apply high-voltage, fast pulsed electricalenergy.

The high-voltage, fast pulsing catheters may be any appropriate length(e.g., between 6 inches and 100 inches, e.g., between 7 inches and 50inches long, etc.) and may have any appropriate outer diameter,including, but not limited to between 1 French (F), e.g., ⅓ mm and 34 F(e.g., 11.333 mm) (between 3 F and 30 F, between 4 F and 15 F, 30 F orless, 25 F or less, 22 F or less, 20 F or less, 18 F or less, 16 F orless, 15 F or less, 14 F or less, 12 F or less, 10 F or less, 9 F orless, 8 F or less, etc.).

Any of these catheters may include one or more lumen, such as but notlimited to one or more guidewire lumen, extending down the length of thedevice, including alone a midline (central lumen) or side lumen. Thesecatheters may be compatible with any appropriate guidewire or guidecatheter, including but not limited to a 0.035″ guidewire.

Any of these catheters may be steerable. For example, in some variationsthe high-voltage, sub-microsecond catheters described herein may includeone or more pull wires or tendons for steering any region of thecatheter, including the distal tip, and/or more proximal regions. Forexample, in some variations, the catheters described herein may beconfigured to include one or more tendon for single-pull articulation.As will be described in greater detail below, the one or more tendons orpull wires may be configured to form part of an electrical pathwaywithin the device.

The shaft of any of the catheters described herein may have a variablestiffness or a constant stiffness, or may include regions of varying orconstant stiffness. In any of the catheters described herein thestiffness may generally be greater at the proximal end than the distalend. Alternatively or additionally, the distal end region (which mayinclude the one or more electrodes, may be stiff or stiffenable (e.g.,by the addition of a stiffening member, guidewire, etc.). Typically, theshaft of the device may be configured to be a torqueable shaft toprovide a user with a full 360 degrees of selective rotation of thedistal tip.

Any of the catheters described herein may be configured to include aforce-applying member at the distal end region of the catheter (e.g., aninflatable balloon, hinged arm, expandable frame, etc.) for applyingforce to secure the one or more electrodes into the tissue and/oragainst the tissue. The force-applying member may be configured to drivethe distal tip region including the electrodes against the tissue at ornear the target tissue. As will be described in greater detail below, insome variations the electrodes and/or the distal end region of thecatheter including the electrodes may be configured to penetrate intothe tissue; in some variations the electrodes may be configured tocontrollably extend or project into the tissue when deployed by the userfrom the proximal end.

The one or more of the lumen of the apparatuses, including catheters,described herein may be used to apply or inject fluid, such as aconductive fluid. The application of a conductive fluid may be helpfulto extend the applied field between the electrodes, or between theelectrodes and the tissue being treated, when operating the apparatusesdescribed herein. Conductive fluid may also or alternatively be used totransfer the field between the electrode and/or the tissue to improvethe electrical contact between a target tissue and the apparatus. Anyappropriate conductive fluid (and/or conductive gel) may be used. Insome applications, for example, cardiac applications, one of the lumensof the catheter may be used to inject saline into a ventricle. In somevariations one lumen or more may be used to deliver a visualizationfluid (e.g., contrast agent, dye, etc.). In some variations, one lumenor more may be used for aspiration (e.g., vacuum). In some variationsone lumen or more may be used for perfusing the tissue, including thetarget tissue.

The catheters described herein may be configured to reduce capacitivecoupling that may otherwise arise from the electrical paths extendingthrough the body of the catheter to the electrodes at the distal end.For example, any of these devices may include a coaxial conductor withinthe shaft to help reduce capacitive coupling effects. Non-coaxialconductors within the catheter shaft are also described herein.

For example, FIG. 4 illustrates one example of a cross-section of aflexible high-voltage, sub-microsecond catheter. In this example, thecatheter includes five concentric layers, including three insulating(dielectric) layers 401, 403, 405 and two conductor layers 407, 409,comprising braided conductors. There is also a central inner lumen 411.The dimensions in millimeters (bracketed), shown on the right side ofthe figure, are for illustration only, and may be separately varied by,e.g., +/−1%, 5%, 10%, 15%, 25%, 50%, 75%, 100%, 150%, 200%, etc. ormore.

In this example, the central inner lumen 411 is configured to becompatible with a standard (e.g., 0.035″) guide wire. The Braid layersmay be, e.g., braids of multiple 0.002″ round SST 304V wire. Anyappropriate braid pattern may be used, and the braid pattern may beadjusted along the length of the catheter to adjust the stiffness(including bending stiffness) of the catheter. For example, the braidmay increase in braid angle of all or some of the number of filamentsforming the braid (e.g. the angle of the braided material relative tothe long axis of the catheter) towards the distal end of the catheter,reducing the relative stiffness of the catheter; the more parallel tothe long axis the greater number of filaments are, the less stiff thecatheter in this region may be. The braid pattern of the more innerlayer 409 may be the same or different from the braid pattern of themore outer conductive layer 407. In some variations it may be beneficialto include braids having different braid angles in inner vs. outerlayers.

The dielectric layers 401, 403, 405 may be, e.g., 0.010″ Fluorinatedethylene propylene (FEP), having, e.g., a dielectric strength of about 2kV/mil. Any appropriate insulating/dielectric material may be used. Inthe example shown in FIG. 4, the outer diameter of the shaft isapproximately 3 mm; as mentioned the catheter may be larger or smaller.

In some variations, two or more additional layers (of, respectively,conductive material, including braided conductive material, andinsulating/dielectric material) may be used (not shown). The thicknessesand orientation of these additional layers may be similar to that shownfor the inner layers. In some variations the inner lumen may bepartitioned, and/or may include one or more additional dedicated regions(e.g., imaging lines, fiber optics, etc.).

The electrodes for applying the high-voltage, fast (e.g., microsecond,sub-microsecond, nanosecond, picosecond, etc.) electrical energy may beconfigured to have any appropriate configuration, including, but notlimited to, needle electrodes, surface electrodes, ring electrodes, bandelectrodes, disc electrodes, etc. For example, in some variations, theelectrodes may have two or more ‘bands’ or rings around the distal endregion of the catheter for delivery of the high-voltage, fast electricalenergy. All or a portion of these rings or bands may be insulated tolimit the application of energy to a particular face or region of theelectrodes. The electrodes may be provided in pairs or a set (e.g., oftwo or more) for the delivery of energy. For example, an array ofelectrodes at the distal end may provide energy to the target tissue. Insome variations the electrodes may be spaced apart from each other by aminimum distance. For example, the spacing between adjacent electrodesconfigured to apply high-voltage, fast electrical energy may be at least0.2 mm, at least 0.3 mm, at least 0.4 mm, at least 0.5 mm, at least 0.6mm, at least 0.7 mm, at least 0.8 mm, at least 0.9 mm, at least 1 mm, atleast 1.2 mm, at least 1.3 mm, at least 1.5 mm, at least 1.7 mm, atleast 2 mm, at least 2.2 mm, at least 2.5 mm, etc.

FIG. 5 is an example of a transverse section of a flexible high-voltage,sub-microsecond non-concentric lumen catheter 500. In FIG. 5, at least aportion or a full length of the catheter may include a non-concentricarrangement of the dielectric insulator and two (or more) electricallines, as shown. In this example, the conductive wires 507, 509 areseparated from each other and from the inner lumen 511 (e.g., guidewirelumen) by a single, large dielectric/insulator 501. The outside of thecatheter may include a braided jacket 505, which may be configured as toadjust/provide torsional stiffness of the catheter; this braided jacketmay be a conductive material (similar to the conductive wires 507, 509),and set to ground and/or it may be non-conductive. It should beunderstood by those skilled in the art that the example of thenon-concentric arrangement of FIG. 5 is just one possible configuration.In other examples, the conductive wires 507 and 509 may be located oneither side of the lumen 511, or they could be combined and run down(e.g., as a twisted pair) a single/larger lumen (not shown). As in FIG.4, the inner lumen 511 may be configured to accommodate a typical 0.035″guide wire. In this example, the dielectric distances may be, e.g.,0.010″ of FEP, for example, and may be conductor-to-conductor,conductors-to-guidewire, and/or conductors-to-braided jacket. In FIG. 5,the outer shaft may be any appropriate dimension, including, e.g., 2.27mm in outer diameter as shown; in some variations the outer diameter maybe reduced if the braid is a non-conducting layer that may be includedwithin the dielectric/insulator 501.

FIG. 6 is another example of a transverse section of a high-voltage,sub-microsecond catheter. In this example, the catheter includes fiveconcentric layers, including three insulating (dielectric) layers 601,603, 605 and two conductor layers 607, 609. The insulating layerinsulate to a minimum of 18 kV (e.g., using 9 or more mil FEP, 6 or moremil of Polyimide, etc.) of insulation around each conductive element. Inthis example, the inner guidewire channel 611 may have an ID of 0.038inches, and an OD of 0.042 inches and be surrounded by the innerdielectric layer 605. The inner conductor layer 609 may be formed of aplurality of braided conductive filaments, as mentioned above. Themiddle dielectric layer 603 may be at least partially surrounded by theouter conductive layer 607, which may also be formed of a plurality ofbraided conductive filaments. In this example, the inner conductivelayer has an OD of 0.050 inches, the middle insulation layer has an ODof 0.080″, the outer conductive layer has an OD of 0.088 inches, and theouter insulating layer 601 has an OD of 0.118 inches. The outer diameterof the catheter is approximately 3 mm.

The electrodes at the distal end of the catheter may be configured towithstand, for example, 3 kV (dielectric strength) or more (e.g., atleast 4 kV, at least 5 kV, at least 9 kV, at least 10 kV, at least 12kV, at least 15 kV, at least 18 kV, at least 20 kV, at least 22 kV, atleast 25 kV, at least 30 kV, etc.). In some variations, the electrodesare configured to withstand a minimum, e.g., for safe delivery ofeffective nano-pulse energy levels, of at least 1 kV (e.g., at least 5kV, at least 9 kV, at least 10 kV, at least 12 kV, at least 15 kV,etc.).

In general the catheters described herein are also configured towithstand torque. For example, in some variations the conductorsconfigured to carry the high-voltage, fast (e.g., sub-microsecond)pulsed electrical energy are woven/braided conductive layers. Thesewoven layers may be, e.g., a metallic braid of conductive filaments,such as stainless steel (e.g., 304V SST), nickel-titanium (Nitinolwires), and/or other conductive filaments. The filaments and/or thebraid pattern may be configured to increase or improve torquability. Forexample, the filaments may be flat (e.g., may have rectangularcross-sectional diameters of between 0.0001 and 0.002 on a short sideand between about 0.0015 inches and 0.006 inches on a longer side, suchas 0.0005″×0.0015″, 0.001″×0.003″, 0.002″×0.006″, etc.). Alternatively,the filaments may be oval, round or rounded (e.g., diameter of betweenabout 0.002 inches and 0.006 inches, etc.). In some variations thenumber of wire crosses per linear inch (“pic count”) may be relativelyhigh, providing a high density, typically low braid angle, or low,providing a lower density, low braid angle. As mentioned above, thebraid angle (e.g., the pic count) may vary along the proximal-to-distallength to control flexibility, kink resistance and torsional stiffness.In some variations the braid pattern may be selected and/or modified(e.g., along the length of the catheter). Any appropriate braid patternmay be used, including a “regular” braid pattern (one over two wires,under two wires, etc.), “diamond” braid pattern (two over two wires,under two wires), “half-diamond” (one over one wire, under one wire,etc.), or the like. The braid pattern may be different along the lengthto provide variations in torsional stiffness and kink resistance.

In any of the catheters described herein a non-metallic material may beused for either or both the conductive layer and/or a non-conductivelayer, that may modify/adjust the mechanical properties of the catheter.For example, any of these catheters may include a non-metallic braidmaterial as a conductive layer and/or a sheath that is made of a Kevlar(e.g., stranded) material, a Polyethylene terephthalate (PET) material,liquid crystal polymer (LCP) monofilament, etc. Non-metallic materialsmay be MRI-compliant.

Any of the catheter devices described herein may include a jacket layer(e.g., an outer jacket), as mentioned above. For example, FIGS. 7A and7B illustrate examples of cross-sections through catheters including anouter jacket 713 surrounding the rest of the catheter. These cathetersare shown having a configuration similar to that shown in FIGS. 4 and 6,described above, although other configurations (including thenon-concentric configurations such as shown in FIG. 5) may be used. InFIGS. 7A and 7B, the catheter includes a central lumen 711, threeinsulating/dielectric layers 701, 703, 705 and two conductive layers707, 709. The outer jacket 713 may be present along all or a portion(e.g., proximal portion) of the catheter; in some variations the jacketmay modify the flexibility of the catheter so that it is relativelystiffer more proximal and relatively more flexible more distally. Thejacket may be formed of any appropriate material, including, but notlimited to thermoplastics (e.g., PU, Nylon, Pebax, etc.), thermosetmaterials (e.g., Silicone, PI, etc.). The jacket may have an outerdiameter that is constant or may vary along the length. For example, theouter diameter may vary from 3 F-30 F. In some variations the cathetermay be made lubricious by including a lubricious material or outercoating (e.g., as part of or applied to the outer surface, including thejacket). The material forming the outer jacket may adjust the durometer(e.g., harness). In any of these variations the outer jacket may beformed of a material that resists physical damage (e.g., puncture,crushing, etc.), which may otherwise interfere with the electricalisolation of the conductive elements of the catheter.

The outer jacket for the catheter may include a braided or coiledmaterial. The braided or coils (e.g., one or more helically woundelements arranged around the circumference of the catheter) may be usedto provide structural support and/or otherwise modify the physicalproperties of the catheter. In some variations the outer jacket regionmay include one or more channels for pull wires (e.g., tendons), fiberoptics (for visualization, illumination, treatment, sensors, etc.),and/or for additional electrical conductors (e.g., low voltage/lowcurrent connectors, e.g., for one or more sensors, etc.). For example,FIG. 7B shows an example of a catheter including an outer jacket 713that is surrounded by a plurality of channels 735. These channels mayinclude (and/or be filled with) one or more pull wires, optical fibers,vacuum lines, injection ports for conductive fluid, etc. as mentioned.When pull wires are used, the pull wire may be any appropriate material(e.g., stainless steel, stranded cable, stranded polymer, e.g., Dyneema,etc.). A pull wire may extend down the entire length of the catheter (tothe distal end) or it may terminal before the distal end of the catheterto provide bending in particular location. Multiple pull wires may bearranged in positions around the perimeter of the catheter eithersymmetrically or asymmetrically. The central lumen 711 in both FIGS. 7Aand 7B may also be used to pass one or more elements, including, but notlimited to, a guidewire. Either or both the inner walls of the centrallumen and/or peripheral channels may be lined or coated with a material,such as a polymeric material, lubricious material, etc., including aTeflon material. In some variations the outer jacket is the same as theouter insulator/dielectric layer 701.

Any of these catheters may include a stacked coil tube configured toprevent compression of the shaft during articulation.

Conductors, including the conductive layers, for conducting thehigh-voltage, fast pulse (e.g., sub-microsecond) energy may be strandedconductors, as described above, however in some variations theconductors may also include one or more solid cores, which may belarger-diameter strands, etc.

Any of the catheters described herein may be configured to articulate,e.g., by pulling and/or pushing one or more tendons, by inserting acurved or bendable steering element through a lumen, etc. In somevariations the catheter includes a jacket or other layers (including theconductive layers) with different materials, different durometers, etc.to vary the stiffness and the provide regions for localizedarticulation, including articulation of specific segments of the shaft(e.g., the distal tip region).

FIGS. 8A-8D illustrate example of catheters having one or more pullwires. For example, in FIG. 8A, a cross-section of a catheter showing apull wire 838 on the top. The catheter includes two non-concentricconductors 807, 809, and a central channel 811 (e.g., for a guidewire)as well as a surrounding insulator/dielectric material 803. Anadditional outer jacket 813 may also be included. In variations having asingle pull wire 838, the device may be biased to return to a shape(e.g., linear shape, curved shape, etc.) so that releasing tension onthe pull wire allows the catheter to resume a pre-set shape. FIG. 8Bshows a similar catheter with a pair of pull wires 838, 838′ on oppositesides of the catheter. In some variations, a catheter may include three(e.g., separated by 120 degrees) or more (four, five, six, etc.) pullwires. FIGS. 8C and 8D show similar examples with concentric conductivelayers 807, 809 and insulating/dielectric layers 801, 803, 805,surrounding the central opening 811.

FIGS. 9A-9C illustrate bending of a high-voltage, sub-microsecondpulsing catheter as described herein. In FIG. 9A, a cross-sectional viewof the catheter 900 is shown, showing two conductive layers 907, 909concentrically arranged along the length of the catheter and eachconnecting to an electrode 917, 919 on the outer lateral surface of thecatheter. The insulating layers 901, 903, 905 may surround theconductive layers and may be sufficiently thick and have dielectricproperties allowing them to insulate, depending on particularrequirements or application, for example to greater than 1 kV (e.g., 2kV or more, 3 kV or more, 5 kV or more, 8 kV or more, 9 kV or more, 10kV or more, 12 kV or more, 15 kV or more, etc.). FIG. 9B shows across-section of the catheter through line B in FIG. 9A. Two tendons 938and 938′ (pull wires) may be used to articulate the catheter, as shownin FIG. 9C, showing bending in two directions. This bending may be usedto help navigate the catheter and may also be used to help drive thecatheter against a target tissue, as described in more detail below.

The catheters described herein may have an increasepushability/trackability to provide column strength whenbending/advancing the catheter. Catheters with more flexible distal endsmay have improved performance when, e.g., crossing tortuous anatomy toreach a target treatment region. In some variations all or a portion ofthe length of the catheter may be configured to have a braidedconstruction (as described above) modifying the flexibility, one or morecoils or coil tubes (including stacked coils) to modify the flexibility,one or more cut hypotubes (e.g., to vary the flexibility, torqueproperties, etc.) or the like.

The catheters devices described herein may be used with one or moreaccessory devices, including, but not limited to guidewires of anyappropriate size (e.g., 0.14 inch diameter, 0.018 inch diameter, 0.035inch diameter, etc.) or material (nickel titanium, stainless steel,polymer, etc.), including steerable guidewires. These catheters may alsobe used with an introducer sheath (e.g., 4 F-12 F, sized by internaldiameter, or other appropriate sizes), a transseptal sheath, a trocar(e.g., 3, 5, 10 mm trocar), and may be used with or form part of anendoscope (e.g., colonoscope, bronchoscope, gastroscope, etc.).

Any of the catheters described herein may include a bias that may beactuated to drive the electrode(s) against the target tissue and/or intothe tissue to reach the target tissue. FIG. 10A-10C illustrates oneexample of a catheter configured to deliver high-voltage, fast pulse(e.g., sub-microsecond) energy to a target tissue. In FIG. 10A a crosssection through the catheter shows a central lumen 1011 concentricallysurrounded by three insulating layers 1001, 1003, 1005 themselvessurrounding two conductive layers 1007, 1009. An outer inflatableballoon 1041, having an inflatable lumen 1044 at least partiallysurrounds the catheter (e.g., a distal tip region of the catheter). Thisballoon may be inflated to drive the electrodes (not visible in FIG.10A) against the tissue, as shown in FIGS. 10B-10C. In FIG. 10B theballoon 1041 is deflated, while in FIG. 10C the balloon may be inflated(e.g., by saline) and may push against a vessel wall (not shown) todrive the electrodes 1017, 1019 against the target tissue. Theelectrodes may be separated by an electrically insulating material 1022to a minimum separation distance (e.g., 0.5 mm, 1 mm, 3 mm, 4 mm, 5 mm,6 mm, etc.). In some variations the balloon material may be electricallyinsulating. The balloons may be formed of a low-compliance material(e.g., Pebax, Nylon, PET, etc.) or a high-compliance material (e.g., PU,silicone, TPEs such as chronoprene, polyblend, etc.), and may have burstpressures of greater than 30 atm. In some variations (not shown in FIG.10A-10C) the electrodes may be on the balloon outer surface.

The catheter may be configured for ablation, including ablating tissuesuch as cardiac (e.g., left atrial ablation) tissues, lung tissueesophageal, gastric, etc., including tumors. For example, theapparatuses described herein may be used to treat, e.g., the bronchialpassages to reduce mucus to treat COPD or bronchitis, emphysema, etc.FIG. 11 illustrates one example of a catheter device configured forablating cardiac tissue, including a plurality of band electrodes 1117along the outer length of the catheter 1100. The distal end of the shaftmay be highly flexible, as shown.

In general, the one or more electrodes may be positioned on the distaltip of the catheter and may be configured to prevent make electricalcontact with the target tissue, while avoiding electrical contact withnon-tissue, electrical interference and/or arcing. One or moreelectrodes may be connected to the conductive layers. For example, FIG.12A shows one example of a catheter 1200 having a pair of ringelectrodes 1217, 1219 each connected to conductive layer 1207, 1209. Thecatheter has a tissue-penetrating distal tip 1239, and may be used,e.g., to penetrating a tissue such as a tumor, to apply treatment.

Although the majority of the catheters described herein include one ormore sets of electrode pairs on the lateral side of the catheter,typically at or near the distal tip, in some variations one or moreelectrodes may be positioned facing distally from the distal tip of theelectrode. For example, FIGS. 12B and 12C illustrate examples ofcatheters having electrodes at the distal tip that face distally. InFIG. 12B, the distal-facing electrodes 1217, 1219 are connected as ringelectrodes on the tissue-penetrating distal end of the catheter; in somevariations at least a portion of this distal facing ring may beinsulated, reducing the size of the distal-facing electrodes. In FIG.12C, for example, smaller distal-facing electrodes 1217″, 1219″ areexposed. FIGS. 12A-12C shows examples of catheters having pointed (e.g.,tissue-penetrating) distal tips that may be used, for example, with aguide wire that may penetrate the tissue, such as a tumor. Thedistal-facing electrodes may also be used with non-tissue penetratingtips. In addition, the electrodes themselves may be tissue-penetrating,and may be configured to extend from the catheter into the tissue whendeployed.

FIG. 13 shows an example of a system 2600 including a catheter 2620 thatmay be used to deliver high-voltage, fast pulse energy to a targettissue, for example to contact a patent with terminals percutaneously orendoluminally during treatment. In this example, the catheter 2620includes tissue-penetrating electrodes 2622 that extend from the distalend region of the catheter which itself extends from an endoscope 2610.For example, catheter 2620 may be routed through a lumen in theendoscope 2610. The catheter 2620 includes electrically insulatingportions 2626 and positive and negative electrically conductiveelectrodes 2622. In some embodiments, catheter 2620 also includes orallows passage of a guide wire (or flexible needle) 2628 to helppenetrate through tissue. Any of the catheters described herein mayinclude a thermocouple thermally connected to either of its terminals.

Although many of the examples illustrated above show only two conductivelayers, in some variations, multiple conductors (e.g., conductivelayers) may be included, and may allow multiple different sets ofelectrodes to be separately actuated. For example, additional conductivelayers may be concentrically arranged. In some variations the conductivelayer may be divided up into helically arranged (and separate)conductive regions for separately actuating electrodes.

The catheters described herein, and particularly the configuration ofthe conductive and insulating portions may be configured to preventelectromagnetic interference (EMI) even at the high voltages and rapidpulse rates (e.g., sub-microsecond pulsing) used herein. In particular,EMI may be problematic for electronics on or adjacent to the catheter,including robotic delivery systems, sensors, and the like. For rapidpulsing, including nanosecond and sub-nanosecond pulsing, it may beundesirable to widely separate the leads (e.g., positive and negativeleads), as this may result in EMI issues in some configurations,including poorly controlled or incorrect impedance. Thus, in somevariations of the catheters described herein, the conductive leads(e.g., conductive layers) may be arranged to reduce electrical looparea, to prevent radiation of energy (e.g. in which the lead may act asan antenna). Traditional conductive wires may be twisted together(forming a twisted pair) so that any field that is generated by thespace between the conductive lead changes polarity as it extends alongthe length, and at a reasonable distance from the conductive lead thefield is more effectively cancelled. However, the faster the pulsing,the greater the number of twists/inch that may be needed to effectivelyreduce emitted radiation; further, twisting the cables in this mannermay require a large wall thickness. Thus, in some variations, thecatheters described herein may use positive and negative leads in acoaxial configuration, as shown above. In some variations the cathetersare configured to have a coaxial impedance that remains relatively high;even with smaller electrodes, the impedance between the catheterelectrodes may be within the 200-ohm range.

For example, two coaxial braids may be used, one for the positive leadand the second for the negative lead. This may minimize EMI during thehigh-powered rapid (e.g., nanosecond) pulsing. Further, the impedancemay be better controlled, enabling more reliable pulse and powerdelivery to the electrodes. As mentioned above, this configuration maybe used with one or more additional wires extending in the conductivelayer (e.g., within the braid, which may also have structuralsignificance to the catheter's mechanical properties) without negativelyimpacting the control of impedance and the reduction in EMI.

In some variations, the conductive layer may be formed of a braid ofconductive fibers that are also braided with an insulator (e.g., carbonfiber) and a good conductor to adjust the impedance. The cablecharacteristic impedance is typically the square root of theinductance/unit length (L) along the conductors divided by thecapacitance/unit length (C) between the conductors. For two (or more)coaxial braids, as opposed to a coaxial cable, the L is smaller due tothe wide conductors and the C is larger due to the increased surfacearea between the conductors. So, the braid impedance may be quite low,e.g., in the 20-ohm range. This potentially very low characteristicimpedance can be increased by using very thin braid material, increasingL or using a conductive material for some of the braid strands, whichcan increase C. For example, a braid may be configured to achievecharacteristic impedances from 20-ohms to ˜150-ohms. For lower pulsevoltage requirements (e.g., less than 5 kV, likely ≤2.5 kV) andpotentially lower currents, a partially-conductive but uniformlydistributed braiding (with insulating braid material making up much ofthe weave) could achieve ˜150 to 200-ohm impedance and still have lowenough resistance and good dispersion properties (dispersion is pulsewidth distortion cause by the higher-frequency pulse spectrum componentsattenuating more and propagating slower, phase shifting differently,than the lower-frequency components).

In any of these variations the catheter may include a high-voltageconnection to the catheter. In some variations the catheter may includea high-voltage connector on the attachment to the pulse generator and/ora hand piece. In some variations, the device may include multiple (e.g.,2, 3, 4, 5, 6, etc.) connections at the interface with the pulsegenerator and/or hand piece. These connectors as well as the cathetersmay therefore meet minimum electrical insulation requirements andstandoff of the high voltages from the fast pulsing (e.g.sub-microsecond, nanosecond, picosecond, etc. pulsing).

Connectors

FIGS. 14A and 14B are illustrations of one example of a high-voltageconnector 2700 configured to be mated with a pulse generator (e.g., ahousing cutaway portion 2750 of a pulse generator), as shown in FIG. 1.Connector 2700 may, for example, be used in system 100 to connectcatheter 102 to housing 105. When mated, connector 2700 electricallyconnects the catheter 102 with the electronic components internal tohousing 105, such as a pulse generator configured to deliverhigh-voltage, very fast (e.g., sub-microsecond) pulses. FIG. 14Aillustrates connector 2700 and cutaway portion 2750 in an unmatedposition. FIG. 14B illustrates connector 2700 and cutaway portion 2750in a mated position.

Connector 2700 may include a hole 2702 configured to receive a cableelectrically contacting a catheter. Connector 2700 also includes ahandle 2706 which includes internal conductors which electricallyconnect terminals 2704 with the cable. Handle 2706 can also include aninsulating safety structure, such as a standoff skirt 2708, which isconfigured to provide at least a minimum clearance distance d_(min-user)along a surface of connector 2700 between a user's hand holding theconnector 2700 by the handle 2706 (e.g., by a hand-grip portion of thehandle in those applications where the device is hand-held) andterminals 2704 without increasing the total length of the connector 2700or the actual physical distance between the terminals 2704 and alocation on the handle of the connector where the user may place his orher hands or fingers.

A “minimum clearance distance from the user's hands” (d_(min_user)) asused herein may include a shortest distance that avoids an arc in boththe air and along an insulative material surface path to a grip portionfor a user's hand. In other words, d_(min_user) includes a distance thatis a greater of the following two distances: 1) a shortest distance orpath that prevents an arc between two conductive parts measured alongany surface or combination of surfaces of an insulating material, and 2)a shortest path in air between two conductive parts that prevents anarc. Addition of a standoff skirt, like the skirt 2708, also allows oneto reduce the total length of the connector while providing a desiredd_(min_user).

In some embodiments, the minimum clearance distance is equal to orgreater than 0.5, 0.85, 1.0, 1.27, 2.5, 3.2, 3.8, 4.4, 5.1, 6.4, 7.6,10.2, 12.7, or more centimeters (i.e., 0.20, 0.33, 0.39, 0.5, 1, 1.25,1.5, 1.75, 2, 2.5, 3, 4, 5, or more inches).

As shown, terminals 2704 may be spaced apart from handle 2706 by spacers2710, for example, by a distance greater than 1 inch. As shown, housingcutaway portion 2750 may include terminal receptacle holes 2752, whichare configured to receive terminals 2704 of connector 2700 whenconnector 2700 is mated with housing cutaway portion 2750. In thisembodiment, housing cutaway portion 2750 also includes one or more skirtreceptacle holes 2754, which is configured to receive standoff skirt2708 of connector 2700 when connector 2700 is mated with housing cutawayportion 2750.

To increase the distance of a shortest path along the surface ofconnector 2700 between electrically conductive terminals 2704 and theuser's hand, in this embodiment, standoff skirt 2708 includes twoconcentric ring portions. The concentric ring portions surround bothspacers 2710 and may be centered between the two spacers 2710. Inaddition, housing cutaway portion 2750 includes two skirt receptacleholes 2754. In alternative embodiments, a connector has just one or morethan two concentric ring portions and a corresponding housing cutawayportion has just one or more than two skirt receptacle holes.

FIGS. 15A, 15B, 15C, and 15D are illustrations of a cross-sectional viewof connector 2700 and housing cutaway portion 2750. The plane of thecross-sectional view is defined by the axis of the terminal receptacleholes 2752 illustrated in FIG. 14A. FIG. 15A illustrates connector 2700and cutaway portion 2750 in an unmated position. FIGS. 15B and 15Cillustrate connector 2700 and cutaway portion 2750 in a mated position,where FIG. 15C illustrates in detail F an enlarged view of portions ofconnector 2700 and cutaway portion 2750. The connector may be integratedinto any of the catheters described herein, at a proximal end and/orfollowing a handle also coupled to the catheter.

As shown in FIG. 15A, connector 2700 includes cavity 2720 configured toinclude wiring (not shown) which electrically connects the cable withterminals 2704. Cavity 2720 may also include wiring to connect to one ormore thermocouples connected to one or more of the terminals of thecatheter.

Housing cutaway portion 2750 may include female terminals 2760 (FIG.15A) which are configured to receive male terminals 2704 when connector2700 and housing cutaway portion 2750 are in the mated position. Setbackdistance 2761 is from a face of the housing cutaway portion 2750 toterminals 2760.

Housing cutaway portion 2750 may also include cavities 2770 which areconfigured to include wiring (not shown) which electrically connectsterminals 2760 with the electronic components internal to the housing.As a result, when in the mated position, the electronic componentsinternal to the housing are electrically connected with a therapeuticcatheter via terminals 2760, terminals 2704, wiring between terminals2704 and a cable, and the cable, which is electrically connected to thetherapeutic catheter.

Housing cutaway portion 2750 also illustrates electromechanical switch2780. As a result of connector 2700 and housing cutaway portion 2750being in the mated position, electromechanical switch 2780 assumes aconductive state indicating that the connector 2700 and the housingcutaway portion 2750 are mated. In addition, as a result of connector2700 and housing cutaway portion 2750 being in an unmaintained position,electromechanical switch 2780 assumes a conductive state indicating thatthe connector 2700 and the housing cutaway portion 2750 are unmated.Electromechanical switch 2780 may be connected to a controller (notshown) which may be configured to prevent electronic components internalto the housing from applying electrical signals to terminals 2760 as aresult of connector 2700 and housing cutaway portion 2750 being unmated,or may be configured to allow electronic components internal to thehousing to apply electrical signals to terminals 2760 as a result ofconnector 2700 and housing cutaway portion 2750 being mated.

In some embodiments, electromechanical switch 2780 includes circuitryconfigured to interface with the controller. For example, the controllermay identify the connector 2700 or a catheter connected to the connector2700 as a result of the controller receiving identifying informationfrom the circuitry. In some embodiments, the circuitry may be configuredto count and store the number of high-voltage, fast pulsing (e.g.,sub-microsecond pulsing) pulses delivered through the connector 2700.

FIG. 15D illustrate examples of minimum clearance distances. Femaleterminals 2760 provide electrical power to male plug terminals 2704.Terminals 2760 are shielded from or are spaced a minimum clearancedistance d_(min_user) 2898 apart from external portions of the housingwhich may be accessed by a hand or a finger of a user. The minimumclearance distance may be determined based at least in part on anexpected voltage applied to terminals 2760 to ensure that the voltage isinsufficient to cause a shock to a hand or finger of the user if placedthe minimum clearance distance from the terminals 2760.

Minimum clearance distance 2898 to the user is measured by followingsurfaces out of the receptacle's holes, around dual skirts 2708, and toa user, as a hand of a user may be placed next to a visible seam betweenthe connector 2700 when mated with the housing cutaway portion 2750 asshown. In some embodiments, the minimum clearance distance is at least0.5, 0.85, 1.0, 1.27, 2.5, 3.2, 3.8, 4.4, 5.1, 6.4, 7.6, 10.2, 12.7, ormore centimeters (i.e., 0.20, 0.33, 0.39, 0.5, 1, 1.25, 1.5, 1.75, 2,2.5, 3, 4, 5, or more inches).

FIG. 15D also shows an example of another minimum clearance distance2899, which represents minimum clearance distance between terminals(d_(min_terminals)). This distance d_(min_terminals) is described inmore detail in references to FIG. 16. Either minimum clearance distancecan be equal to or greater than 0.5, 0.85, 1.0, 1.27, 2.5, 3.2, 3.8,4.4, 5.1, 6.4, 7.6, 10.2, 12.7, or more centimeters (i.e., 0.20, 0.33,0.39, 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, or more inches).

FIG. 16 is an illustration of connector 2900 configured to be mated withhousing cutaway portion 2950. Connector 2900 may, for example, be usedin a high-voltage, fast pulsing (e.g., sub-microsecond pulsing) system100 to connect catheter 102 to housing 105. When mated, connector 2900electrically connects catheter 102 with the electronic componentsinternal to housing 105, such as a high-voltage, fast pulsing (e.g.,sub-microsecond pulsing) pulse generator.

FIG. 16 illustrates connector 2900 and cutaway portion 2950 in anunmated position. As a comparison of exemplary embodiments, FIGS.14A-14B illustrates insulative structures, such as the skirt 2708,configured to provide a minimum clearance distance between the user'sfingers and/or hand and the conductive terminals. FIG. 16 illustratesadditional novel features configured to provide a minimum clearancedistance 2899 between the conductive terminals themselves, such as aminimum clearance distance d_(min_terminals), shown in FIG. 15D. Theminimum clearance distance d_(min_terminals) provides protection againstan arc between the conductive terminals and protects, for example, apatient.

The “minimum clearance distance between the terminals”(d_(min_terminals)) as used herein includes a shortest distance thatavoids an arc both in the air or along an insulating material surfacepath. In other words, d_(min_terminals) can include a distance that isthe greater of the following two distances: 1) a shortest distance orpath that prevents an arc between two conductive parts measured alongany surface or combination of surfaces of an insulating material, and 2)a shortest path in air between two conductive parts that prevents anarc.

A “creepage distance” include a shortest distance that prevents arcsalong the surface of the insulating material between two conductiveparts, as defined by the International Electrotechnical Commission(IEC), or as otherwise known in the art. It can include the surfacedistance from one conductive part to another conductive part or an areaaccessible by a user.

“Air clearance” includes the shortest path that prevents arc in airbetween two conductive parts as defined by the IEC, or as otherwiseknown in the art. It can include the uninterrupted distance through theair or free space from one conductive part to another conductive part oran area accessible by a user.

Connector 2900 can include features similar to or identical to connector2700 illustrated above in FIGS. 14A, 14B, 15A, 15B, and 15C. Connector2900 includes standoff skirt 2908, which is similar to standoff skirt2708 of connector 2700. In addition, connector 2900 includes additionalstandoff skirts 2909. As shown, standoff skirts 2909 each surround aportion of one of the spacers 2910. Standoff skirts 2909 maintain adesired separation between terminals 2904. Housing cutaway portion 2950can include features similar to or identical to housing cutaway portion2750 illustrated above in FIGS. 14A, 14B, 15A, 15B, 15C, and 15D.

In this embodiment, in addition to terminal receptacle holes 2952 andskirt receptacle hole 2954, housing cutaway portion 2950 also includesskirt receptacle holes 2956, which are configured to receive skirts 2909of connector 2900 when connector 2900 is mated with housing cutawayportion 2950.

FIGS. 17A and 17B are illustrations of a cross-sectional view ofconnector 2900 and housing cutaway portion 2950. FIGS. 17A and 17Billustrate connector 2900 and cutaway portion 2950 in a mated position,where FIG. 17B illustrates in detail H an enlarged view of portions ofconnector 2900 and cutaway portion 2950.

In some embodiments, a high-voltage, fast pulsing (e.g., sub-microsecondpulsing) pulse generator may be connected with a cable to a therapeuticcatheter, where the therapeutic catheter has terminals which areelectrically connected to the cable by a connector/receptacle matinghaving characteristics similar or identical to one or more of connector2700 and housing cutaway portion 2750 and connector 2900 and housingcutaway portion 2950.

For example, FIG. 18 illustrates an intermediate connector 3100 whichhas therapeutic terminals (electrodes) which are connected to cable 3150through conductors which run through catheter handle (or handle) 3110and catheter 3120. The intermediate (handle) connector 3100 may be usedin the high-voltage, fast pulsing (e.g., sub-microsecond pulsing)treatment systems discussed herein. For example, cable 3150 may beconnected to a high-voltage, fast pulsing (e.g., sub-microsecondpulsing) pulse generator by another high-voltage connector (not shown)having features similar or identical to those of the connectorsdiscussed elsewhere herein; the catheter may therefore be connected viaa connector directly to the pulse generator or through an intermediateconnector (e.g., connecting to a handle of the catheter, where one isincluded, as shown in FIG. 18.

As shown, the proximal end of the catheter 3120 may be removablyconnectable to a handle 3110. To connect catheter end 3120 to handle3110, connection terminals 3160 may be inserted into skirt 3130. In someembodiments, the catheter end 3120 may be disposable, or may bediscarded or disposed of after a single use.

Any of the apparatuses, including catheters and systems using them, mayinclude one or more safety interlocking features to prevent the deliveryof the high-voltage, very fast (e.g., sub-microsecond) pulsing until andunless the catheter is properly deployed and in contact with a tissue,e.g., target tissue. For example, the methods and apparatuses describedherein may be configured to emit one or a pattern of test pulses at verylow power (e.g., low voltage) including at high speed (e.g.,sub-microsecond) to detect one or more properties of the electricalpathway including appropriate contact with a target tissue. In somevariations, the apparatus may be configured to determine and detect theimpedance at the one or more pairs of electrodes of the catheter toconfirm that the contact with the tissue (and the electrical pathwayfrom the pulse generator to the tissue) are correct. Thus, theseapparatuses and methods of use may include measuring an impedance of thetissue with the electrodes (e.g., surface electrodes, needle electrodes,knife electrodes, etc.). In some examples, the electrodes can be used tomeasure the impedance of the target tissue to be treated as well as thesurrounding tissue. For example, electrical energy can be applied to thetarget tissue at a known frequency. In a first example, the electricalenergy can initially be a low-voltage pulsed energy until the electrodesare positioned appropriately against or within the target tissue. Thisproper positioning can be confirmed with the impedance measurement. Oncethe electrodes are positioned within or against the target tissue, theelectrical energy can comprise high-voltage, fast pulsed energy, such assub-microsecond pulses. However, it should be understood that in someapplication and embodiments any type of pulsed electrical energy can beapplied to the target tissue (microsecond, nanosecond, picosecond,etc.).

During treatment of the tissue, treatment may continue if certainconditions are met, but may otherwise be terminated. For example, when achange in the impedance of the target tissue exceeds an impedancethreshold, treatment may stop. Thus, the detection of contact and/ortreatment may be ongoing during a treatment as well as before atreatment. For example, applying electrical energy to the tissue canchange the impedance of the target tissue by breaking down the tissueitself. This change can be measured, and when the change in impedanceexceeds an impedance threshold that indicates the tissue breakdown, theelectrodes can be moved within the tissue or the treatment stopped. Inanother example, because the target tissue (e.g., tumor) may havedifferent impedance from the surrounding tissue, a change in theimpedance may occur because of the location of the catheter andelectrodes relative to the target tissue. Therefore, this change can bemeasured, and when the change in impedance exceeds an impedancethreshold that indicates that location of the electrodes is outside thetarget tissue, the electrodes can be moved or the treatment stopped. Themovement of electrodes can occur either during each pulse or in betweenpulses, or during entire application of the electric energy. Theimpedance threshold may be, for example, between 0.1 kOhms and 100kOhms, such as about 90 kOhms, about 80 kOhms, about 70 kOhms, about 60kOhms, about 50 kOhms, about 40 kOhms, about 30 kOhms, about 25 kOhms,about 20 kOhms, about 15 kOhms, about 10 kOhms, about 5 kOhms, about 2.5kOhms, about 1 kOhm, etc.).

The catheters and systems disclosed may be used in various methods andapplications. For example, some of the methods comprise methods ofdelivering pulsed power to any of the apparatuses described herein,including in particular to a catheter. For example, a method mayinclude: connecting a high-voltage connector to a first conductive layerand a second conductive layer of a catheter, the first conductive layerformed from a first plurality of filaments extending down at least aportion of a length of an elongate body of the catheter, the secondconductive layer formed from a second plurality of filaments extendingconcentric to the first conductive layer. The method may furthercomprise applying a plurality of electrical pulses having an amplitudeof 1 kV or more from the high-voltage connector through the firstplurality of filaments and through the second plurality of filaments,wherein the first and second conductive layers are insulated by aflexible insulating material having a dielectric strength sufficient towithstand 2 kV or more. In some embodiments the electrical pulses mayhave an amplitude of between 1 kV and 15 kV, or between 1 kV and 9 kV,or any sub-range within the above ranges.

Further methods according to the present disclosure comprise methods oftreating tissue. For example, the method of treating tissue maycomprise: inserting a distal end of a catheter into a body, wherein thecatheter comprises at least two electrodes at a distal end region;applying a plurality of electrical pulses having an amplitude of greaterthan 0.1 kV and a duration of less than 1000 nanoseconds to a proximalend of the catheter through a first plurality of filaments extending atleast partially down the length of the catheter and through a secondplurality of filaments extending at least partially down the length ofthe catheter; and delivering the applied plurality of electrical pulsesto the body from a first electrode of the at least two electrodes inelectrical communication with the first plurality of filaments and asecond electrode of the at least two electrodes in electricalcommunication with the second plurality of filaments, wherein the firstand the second plurality of filaments is configured and insulated towithstand 3 kV or more. The second plurality of filaments may extendconcentrically over the first plurality of filaments.

As mentioned above, any of the apparatuses described herein may beimplemented in robotic systems that may be used to position and/orcontrol the electrodes during a treatment. For example, a system mayinclude a robotic arm to which is coupled the catheter. Various motorsand other movement devices may be incorporated to enable fine movementsof an operating tip of the applicator in multiple directions. Therobotic system and/or catheter may further include at least one imageacquisition device (and preferably two for stereo vision, or more) whichmay be mounted in a fixed position or coupled (directly or indirectly)to a robotic arm or other controllable motion device.

Embodiments of the methods of the present disclosure may be implementedusing computer software, firmware or hardware. Various programminglanguages and operating systems may be used to implement the presentdisclosure. The program that runs the method and system may include aseparate program code including a set of instructions for performing adesired operation or may include a plurality of modules that performsuch sub-operations of an operation or may be part of a single module ofa larger program providing the operation. The modular constructionfacilitates adding, deleting, updating and/or amending the modulestherein and/or features within the modules.

In some embodiments, a user may select a particular method or embodimentof this application, and the processor will run a program or algorithmassociated with the selected method. In certain embodiments, varioustypes of position sensors may be used. For example, in certainembodiment, a non-optical encoder may be used where a voltage level orpolarity may be adjusted as a function of encoder signal feedback toachieve a desired angle, speed, or force.

Certain embodiments may relate to a machine-readable medium (e.g.,computer readable media) or computer program products that includeprogram instructions and/or data (including data structures) forperforming various computer-implemented operations. A machine-readablemedium may be used to store software and data which causes the system toperform methods of the present disclosure. The above-mentionedmachine-readable medium may include any suitable medium capable ofstoring and transmitting information in a form accessible by processingdevice, for example, a computer. Some examples of the machine-readablemedium include, but not limited to, magnetic disc storage such as harddisks, floppy disks, magnetic tapes. It may also include a flash memorydevice, optical storage, random access memory, etc. The data and programinstructions may also be embodied on a carrier wave or other transportmedium. Examples of program instructions include both machine code, suchas produced by a compiler, and files containing higher level code thatmay be executed using an interpreter.

Any of the methods (including user interfaces) described herein may beimplemented as software, hardware or firmware, and may be described as anon-transitory computer-readable storage medium storing a set ofinstructions capable of being executed by a processor (e.g., computer,tablet, smartphone, etc.), that when executed by the processor causesthe processor to perform or control performing of any of the steps,including but not limited to: displaying, communicating with the user,analyzing, modifying parameters (including timing, frequency, intensity,etc.), determining, alerting, or the like. In some exemplary embodimentshardware may be used in combination with software instructions toimplement the present disclosure.

When a feature or element is herein referred to as being “on” anotherfeature or element, it can be directly on the other feature or elementor intervening features and/or elements may also be present. Incontrast, when a feature or element is referred to as being “directlyon” another feature or element, there are no intervening features orelements present. It will also be understood that, when a feature orelement is referred to as being “mounted”, “connected”, “attached” or“coupled” to another feature or element, it can be directly mounted,connected, attached or coupled to the other feature or element orintervening features or elements may be present. In contrast, when afeature or element is referred to as being “directly mounted”, “directlyconnected”, “directly attached” or “directly coupled” to another featureor element, there are no intervening features or elements present.Although described or shown with respect to one embodiment, the featuresand elements so described or shown can apply to other embodiments. Itwill also be appreciated by those of skill in the art that references toa structure or feature that is disposed “adjacent” another feature mayhave portions that overlap or underlie the adjacent feature.

Terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting. For example, asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items and may beabbreviated as “/”.

Spatially relative terms, such as “under”, “below”, “lower”, “over”,“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if a device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of over and under. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly”, “downwardly”, “vertical”, “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

Although the terms “first” and “second” may be used herein to describevarious features/elements (including steps), these features/elementsshould not be limited by these terms, unless the context indicatesotherwise. These terms may be used to distinguish one feature/elementfrom another feature/element. Thus, a first feature/element discussedbelow could be termed a second feature/element, and similarly, a secondfeature/element discussed below could be termed a first feature/elementwithout departing from the teachings of the present apparatuses andmethods.

The terms “comprises” and/or “comprising,” when used in thisspecification (including the claims), specify the presence of statedfeatures, steps, operations, elements, and/or components, but do notpreclude the presence or addition of one or more other features, steps,operations, elements, components, and/or groups thereof. Unless thecontext requires otherwise, “comprise”, and variations such as“comprises” and “comprising,” means various components can be co-jointlyemployed in the methods and articles (e.g., compositions and apparatusesincluding device and methods). For example, the term “comprising” willbe understood to imply the inclusion of any stated elements or steps butnot the exclusion of any other elements or steps.

Any of the apparatuses and methods described herein may include all or asub-set of the components and/or steps, and these components or stepsmay be either non-exclusive (e.g., may include additional componentsand/or steps) or in some variations may be exclusive, and therefore maybe expressed as “consisting of” or alternatively “consisting essentiallyof” the various components, steps, sub-components or sub-steps.

As used herein in the specification and claims, including as used in theexamples and unless otherwise expressly specified, all numbers may beread as if prefaced by the word “about” or “approximately,” even if theterm does not expressly appear. The phrase “about” or “approximately”may be used when describing magnitude and/or position to indicate thatthe value and/or position described is within a reasonable expectedrange of values and/or positions. For example, a numeric value may havea value that is +/−0.1% of the stated value (or range of values), +/−1%of the stated value (or range of values), +/−2% of the stated value (orrange of values), +/−5% of the stated value (or range of values), +/−10%of the stated value (or range of values), etc. Any numerical valuesgiven herein should also be understood to include about or approximatelythat value unless the context indicates otherwise. For example, if thevalue “10” is disclosed, then “about 10” is also disclosed. Anynumerical range recited herein is intended to include all sub-rangessubsumed therein. It is also understood that when a value is disclosedthat “less than or equal to” the value, “greater than or equal to thevalue” and possible ranges between values are also disclosed, asappropriately understood by the skilled artisan. For example, if thevalue “X” is disclosed the “less than or equal to X” as well as “greaterthan or equal to X” (e.g., where X is a numerical value) is alsodisclosed. It is also understood that the throughout the application,data is provided in a number of different formats, and that this data,represents endpoints and starting points, and ranges for any combinationof the data points. For example, if a particular data point “10” and aparticular data point “15” are disclosed, it is understood that greaterthan, greater than or equal to, less than, less than or equal to, andequal to 10 and 15 are considered disclosed as well as between 10 and15. It is also understood that each unit between two particular unitsare also disclosed. For example, if 10 and 15 are disclosed, then 11,12, 13, and 14 are also disclosed.

Although various illustrative embodiments are described above, any of anumber of changes may be made to various embodiments without departingfrom the scope of the disclosure as described by the claims. Forexample, the order in which various described method steps are performedmay often be changed in alternative embodiments, and in otheralternative embodiments one or more method steps may be skippedaltogether. Optional features of various device and system embodimentsmay be included in some embodiments and not in others. Therefore, theforegoing description is provided primarily for exemplary purposes andshould not be interpreted to limit the scope of the apparatuses andmethods as it is set forth in the claims.

Various embodiments may be referred to herein individually orcollectively by the term “invention” merely for convenience and withoutintending to voluntarily limit the scope of this application to anysingle invention or inventive concept, if more than one is, in fact,disclosed. Thus, although specific embodiments have been illustrated anddescribed herein, any arrangement calculated to achieve the same purposemay be substituted for the specific embodiments shown. This disclosureis intended to cover any and all adaptations or variations of variousembodiments. Combinations of the above embodiments, and otherembodiments not specifically described herein, will be apparent to thoseof skill in the art upon reviewing the above description.

What is claimed is:
 1. A catheter apparatus for treating tissue, theapparatus comprising: an elongate body comprising: a first conductivelayer formed from a first plurality of braided or woven filamentsextending down at least a portion of a length of the elongate body; asecond conductive layer formed from a second plurality of braided orwoven filaments extending concentric to the first conductive layer;wherein the first and second conductive layers are enclosed by aflexible electrically insulating material; a first electrode at a distalend region of the elongate body in electrical communication with thefirst conductive layer; a second electrode at the distal end region ofthe elongate body in electrical communication with the second conductivelayer; and a high-voltage connector adapted to couple the first andsecond conductive layers to a pulse generator.
 2. The apparatus of claim1, further comprising a guidewire lumen concentrically surrounded by thefirst and second conductive layers.
 3. The apparatus of claim 1, whereinthe first and second electrodes are separated by 0.5 mm or more.
 4. Theapparatus of claim 1, wherein the first conductive layer comprises afirst braid pattern of conductive filaments that varies along the lengthof the elongate body so that the elongate body is more flexible at thedistal end region.
 5. The apparatus of claim 4, wherein the first braidpattern has a different braid angle along the length of the elongatebody.
 6. The apparatus of claim 1, further comprising a bias on an outersurface of the distal end region of the elongate body configured todrive the distal end region of the elongate body against a vessel wallwhen deployed in a vessel.
 7. The apparatus of claim 6, wherein the biasis an inflatable balloon.
 8. The apparatus of claim 1, wherein theflexible electrically insulating material has a dielectric strengthsufficient to withstand 1 kV or more.
 9. The apparatus of claim 1,further comprising one or more steering tendons within a lumen of theelongate body.
 10. The apparatus of claim 1 wherein the first and secondelectrodes comprise needle electrodes.
 11. The apparatus of claim 1,wherein the apparatus is a cardiac catheter and the first and secondelectrodes comprise ring electrodes.
 12. A system for treating tissue,the system comprising: a catheter comprising: an elongate body having afirst conductive layer formed from a first plurality of filamentsextending down a length of the elongate body, a second conductive layerformed from a second plurality of filaments extending concentric to thefirst conductive layer, wherein the first and second conductive layersare enclosed by a flexible insulating material having a dielectricstrength sufficient to withstand 1 kV or more; a first electrode at adistal end region of the catheter in electrical communication with thefirst conductive layer; a second electrode at the distal end region ofthe catheter in electrical communication with the second conductivelayer; a pulse generator configured to generate a plurality ofelectrical pulses having amplitude of at least 0.1 kV and a duration ofless than 1000 nanoseconds; and a high-voltage connector configured toconnect to the pulse generator through a port, the high-voltageconnector adapted to couple the first and second conductive layers tothe pulse generator.
 13. The system of claim 12, wherein at least one ofthe first and second plurality of filaments comprises braided or wovenfilaments.
 14. The system of claim 12, wherein the catheter comprisesthree concentric layers of insulative material separated by the firstand the second conductive layers.
 15. The system of claim 12, whereinthe first conductive layer comprises a first braid pattern of conductivefilaments that varies along a length of the catheter so that thecatheter is more flexible at the distal end region.
 16. The system ofclaim 15, wherein the second conductive layer comprises a second braidpattern of conductive filaments that varies along the length of thecatheter.
 17. The system of claim 12, wherein the flexible insulatingmaterial has a dielectric strength sufficient to withstand 5 kV or more.18. The system of claim 12, wherein the high-voltage connector comprisesan insulating safety structure configured to provide at least a minimumclearance distance without increasing a total length of the high-voltageconnector.
 19. A method of treating tissue, the method comprising:inserting a distal end of a catheter into a body, wherein the cathetercomprises at least two electrodes at a distal end region; applying aplurality of electrical pulses having an amplitude of greater than 0.1kV and a duration of less than 1000 nanoseconds to a proximal end of thecatheter through a first plurality of filaments extending at leastpartially down a length of the catheter and through a second pluralityof filaments extending at least partially down the length of thecatheter; and delivering the plurality of electrical pulses to the bodyfrom a first electrode of the at least two electrodes in electricalcommunication with the first plurality of filaments and a secondelectrode of the at least two electrodes in electrical communicationwith the second plurality of filaments, wherein the first and the secondplurality of filaments is configured and insulated to withstand 1 kV ormore.
 20. The method of claim 19, further comprising connecting thecatheter to a pulse generator using a high-voltage connector.
 21. Themethod of claim 19, further comprising driving the distal end of thecatheter against a tissue so that the first and second electrodescontact the tissue.
 22. The method of claim 21, wherein drivingcomprises inflating an inflatable balloon on a side of the distal end ofthe catheter.
 23. The method of claim 19, wherein at least one of thesteps of inserting, applying and delivering is performed by a roboticsystem.
 24. The method of claim 19, further comprising checking animpedance between the first electrode at the distal end region of thecatheter in electrical communication with a first conductive layer andthe second electrode at the distal end region of the catheter inelectrical communication with a second conductive layer prior toapplying the plurality of electrical pulses and suspending the applyingof the plurality of electrical pulses until the impedance exceeds animpedance threshold.
 25. The method of claim 24, further comprisingcontinuously checking impedance between the first and second electrodesduring the applying of the plurality of electrical pulses and stoppingthe applying if the impedance falls below the impedance threshold.